This proposal is designed to study aspects of immunoglobulin gene expression by characterizing alterations which have occurred in mouse myeloma cells mutant in their Ig production. Some of these mutations have resulted in altered processing of the nuclear RNA to produce internally deleted cytoplasmic mRNA, lacking a portion but not all of an Ig domain. Some of the deletion mutants do not secrete their altered protein products. Certain aspects of these mutations resemble human heavy chain myeloma diseases. The exact nature of the sequences deleted in the mRNA's and the genomic regions surrounding the mRNA deletions will be determined by molecular cloning and DNA sequencing. The half-lives, cytoplasmic localization and rate of synthesis of the mutants mRNA's will be determined. Understanding how these alterations in the mRNA have occurred will hopefully give insights into the normal RNA processing signals. Other mutants to be studied have undergone a switch of Ig subclass produced. These will be studied by Southern blot analysis, hnRNA analysis and cloning and sequencing in order to determine where and how the gene rearrangement has occurred. These alterations may illuminate the process of normal heavy chain gene class rearrangements or unequal sister chromatid exchange.